Haemophilus abundance is associated with response to sublingual immunotherapy in children with allergic rhinitis

BACKGROUND: The nasal microbiome's role in predicting sublingual immunotherapy (SLIT) efficacy in children with allergic rhinitis (AR) remains unclear. Haemophilus, a Proteobacteria genus linked to respiratory inflammation, is a promising candidate biomarker. OBJECTIVE: To evaluate Haemophilus dynamics as a potential predictor of SLIT response in children with moderate-severe AR. METHODS: In this prospective cohort, 63 children with AR and 40 healthy controls (CG) were enrolled. AR patients were stratified by disease severity (mild [MAR] vs. moderate-severe [MSAR]), with MSAR patients receiving 1-year standardized house dust mite SLIT. Based on >20% reduction in Total Nasal Symptom Score (TNSS), patients were classified as responders (RG, n = 25) or non-responders (NRG, n = 15). Nasal microbiome was profiled via 16S rDNA sequencing. RESULTS: Compared to CG, AR children showed increased alpha diversity (Chao1, p < .05; Shannon, p < .01) and enrichment of Staphylococcus. MSAR patients had significantly higher Proteobacteria abundance, particularly Haemophilus, compared to MAR (LDA score >4, p < .001). After SLIT, RG patients showed normalized microbial evenness (Pielou E index) to CG levels, driven by marked Haemophilus depletion (p < .001). In contrast, NRG patients maintained high Haemophilus abundance. Haemophilus and Moraxella showed strong positive correlation (r = .68, p < .001), with both decreasing in RG post-SLIT. CONCLUSION: Elevated nasal Haemophilus is associated with AR severity, and its depletion correlates with SLIT efficacy. Haemophilus may serve as a clinically actionable microbial biomarker for monitoring SLIT response in pediatric AR, offering a novel precision medicine approach to allergen immunotherapy.